This proposal is designed to examine the effects of in vivo modification of normal tissue repair processes in the lung following a well-defined acute injury such as that induced by cadmium chloride (CdCl2) aerosol inhalation or by a common food additive, butylated hydroxytoluene (BHT); injuries which have been well characterized in this and other laboratories. Injury, which involves an exuberant phase of cell proliferation may be particularly susceptible to the action of certain drugs known to interfere with normal cell reproduction and function. Preliminary studies by the principal investigator suggest that appropriate interference with the usual repair sequence common to most acute lung damage (Type 1 cell injury, followed by Type 11 cell proliferation and transformation) may, under certain conditions, completely suppress the hyperplastic response or, alternatively, produce more severe pathology marked by drastically attenuated alveolar walls, with destruction and enlargement of airspaces resembling, to some degree, emphysema. The objectives of the experiments detailed on this proposal are: 1) to examine the immediate effect(s) of certain drugs on the histological repair process in the lung resulting from acute injury, 2) to determine the response of the injured lung to these drugs when administered at various intervals after the onset of the acute damage, and 3) to attempt to correlate alterations in the acute repair process with the pathogenesis of certain chronic lung injuries. The drugs, colchicine and cycloheximide, have been chosen for use by reason of their well-documented actions on renewing cell populations as well as results obtained in preliminary studies by this investigator. These studies will involve primarily the histopathological evaluation of the modified injury, employing both light and electron microscopy. The injury will also be monitored by measuring the incorporation of labeled precursors such as tritiated thymidine, L-proline and L-leucine by liquid scintillation spectrometry and autoradiography.